Graft-versus-host disease (GVHD) is a debilitating and often fatal immunological condition induced by lymphoid cells "grafted" either experimentally or naturally into an immunoincompetent foreign host. Since children may be subjected to GVHD induced by certain therapeutic measures during the period when the central nervous system (CNS) is developing, it is imperative that the effects of GVHD on the CNS be elucidated and possible mechanisms revealed. In order to characterize such effects, we will assess cerebellar development in (Fischer X DA)F1 hybrid rats injected with parental strain lymphoid cells on the day of birth. The cerebellum is a model for developing CNS because: 1) most of its mitosis is postnatal; 2) the Purkinje cells are differentiating but nonmitotic cells; and 3) we have intensely studied the influence of other stresses on its development. We will assess the effect of GVHD on mitosis, cell accumulation and death (DNA content and labelled thymidine uptake with autoradiography and scintillation counting), cell function (RNA and protein content and their syntheses by labelled precursors), cell migration (autoradiography studies of migration of cells from external to internal granular layer), and individual cell maturation (Golgi-stained Purkinje cells analyzed for somal and dendritic aberrations) Our preliminary results indicate that even before acute wasting is evident, there are cerebellar alterations (DNA, RNA and protein contents and 3H-thymidine uptake are decreased). Possible mechanisms we will investigate include: 1) adrenal corticoids (Does adrenalectomy ameliorate cerebellar alterations?); 2) inflammatory reactions (Can generalized inflammation induce cerebellar changes?); 3) alloantibodies (Can alloantibodies induce cerebellar alterations?); and 4) lymphokines (Are there nonantibody secretory products of immune lymphocytes in sera which decrease proliferation?). The principal questions we expect to answer with this study are: What are the characteristics of cerebellar development during and after GVHD? Do the adrenals modulate non-lymphoid tissue susceptibility to GVHD? Is the factor(s) that acts on the cerebellum lymphocyte- or non-cell-mediated?